Goto Hiroki, Shiraishi Yoshioki, Okada Seiji
Division of Radioisotope and Tumor Pathobiology, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan.
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan.
Explor Target Antitumor Ther. 2024;5(1):208-224. doi: 10.37349/etat.2024.00213. Epub 2024 Feb 28.
Radioimmunotherapy (RIT) is a therapy that combines a radioactive nucleotide with a monoclonal antibody (mAb). RIT enhances the therapeutic effect of mAb and reduces toxicity compared with conventional treatment. The purpose of this review is to summarize the current progress of RIT for treating non-Hodgkin's lymphoma (NHL) based on recent preclinical and clinical studies. The efficacy of RIT targeting the B-lymphocyte antigen cluster of differentiation 20 (CD20) has been demonstrated in clinical trials. Two radioimmunoconjugates targeting CD20, yttrium-90 (Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Although these two radioimmunoconjugates are effective and least toxic, they have not achieved popularity due to increasing access to novel therapies and the complexity of their delivery process. RIT is constantly evolving with the identification of novel targets and novel therapeutic strategies using newer radionuclides such as alpha-particle isotopes. Alpha-particles show very short path lengths and high linear energy transfer. These characteristics provide increased tumor cell-killing activities and reduced non-specific bystander responses on normal tissue. This review also discusses reviewed pre-targeted RIT (PRIT) and immuno-positron emission tomography (PET). PRIT potentially increases the dose of radionuclide delivered to tumors while toxicities to normal tissues are limited. Immuno-PET is a molecular imaging tracer that combines the high sensitivity of PET with the specific targeting capability of mAb. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response.
放射免疫疗法（RIT）是一种将放射性核苷酸与单克隆抗体（mAb）相结合的疗法。与传统治疗相比，RIT增强了单克隆抗体的治疗效果并降低了毒性。本综述的目的是基于最近的临床前和临床研究，总结RIT治疗非霍奇金淋巴瘤（NHL）的当前进展。针对B淋巴细胞分化抗原簇20（CD20）的RIT疗效已在临床试验中得到证实。两种靶向CD20的放射免疫偶联物，钇-90（Y）-伊布替尼-替曲膦（泽瓦林）和碘-131（I）-托西莫单抗（贝沙罗汀），分别于2002年和2003年在美国食品药品监督管理局（FDA）获批用于治疗复发/难治性惰性或转化型NHL。尽管这两种放射免疫偶联物有效且毒性最小，但由于新型疗法的可及性增加以及其给药过程的复杂性，它们并未得到广泛应用。随着新型靶点的发现以及使用诸如α粒子同位素等更新的放射性核素的新型治疗策略的出现，RIT也在不断发展。α粒子的路径长度非常短且线性能量转移高。这些特性增强了肿瘤细胞杀伤活性，并减少了对正常组织的非特异性旁观者反应。本综述还讨论了预靶向RIT（PRIT）和免疫正电子发射断层扫描（PET）。PRIT有可能增加递送至肿瘤的放射性核素剂量，同时对正常组织的毒性有限。免疫PET是一种分子成像示踪剂，它将PET的高灵敏度与单克隆抗体的特异性靶向能力相结合。目前正在开发针对CD20和其他抗原的免疫PET策略。免疫PET的诊疗方法将有助于监测治疗反应。
